Human immunodeficiency virus (HIV) superinfection may be as common as initial HIV infection and is not limited to high risk-populations, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health and the National Institute of Allergy and Infectious Diseases (NIAID).
In the first large-scale study of HIV superinfection in a general heterosexual population, researchers examined the rate of superinfection among a community of sub-Saharan adults. HIV superinfection occurs when an HIV-infected individual acquires a new viral strain that is phylogenetically different from all other detectable viral strains. Superinfection can have detrimental clinical effects as well as accelerated disease progression, and increased HIV drug resistance even among individuals who were previously controlling their HIV infection. The results are featured online in of the Journal of Infectious Diseases.
"We found it remarkable that the rates of superinfection and underlying new HIV infections were equivalent. This raises many interesting questions about the natural immune response and its inability to generate resistance to HIV reinfection," says Thomas Quinn, MD, MS, co-author of the study, an NIAID senior investigator, a professor with the Bloomberg School's Department of International Health and director of the Johns Hopkins Center for Global Health.
"For years there has been great debate regarding the rate of HIV superinfection among populations, and previous studies have focused on individuals exposed to the virus through high-risk sexual activity or intravenous drug use," says Andrew Redd, PhD, lead author of the study and a postdoctoral fellow at the Laboratory of Immunoregulation at NIAID. "We were looking to determine the rate of HIV superinfection among a broader, general population using a novel technique sensitive enough to detect even the lowest levels of circulating HIV strains."
Researchers, in collaboration with colleagues at the NIAID Rocky Mountain Laboratories, the Johns Hopkins Rakai Health Sciences Program in Kalisizo, Uganda, and Makerere University in Kampala, Uganda, used an ultra-deep sequencing technique to examine the blood samples of HIV-infected participants of the Rakai Community Cohort Study. Samples were tested at initial HIV diagnosis and at least one year later, prior to beginning antiretroviral therapy. The rate of superinfection was then compared to an estimated overall HIV incidence rate for HIV-negative individuals during this same time. Of the 149 individuals tested, Quinn and colleagues identified seven cases of HIV superinfection during follow-up and all were initially infected with some variant of HIV subtype D. In addition, the rate of superinfection was 1.44 per 100 persons and consisted of both intersubtype and intrasubtype superinfections, comparable to primary HIV incidence in initially HIV-negative individuals in the general population in Rakai.
"These results also have significant implications for estimations of the age of the HIV epidemic and for phylogenetic modeling of viral evolution because many of these models assume that superinfection is not occurring," suggest the authors. "In addition, the finding that superinfection is common and occurs within and between HIV subtypes suggests that the immune response elicited by primary infection confers limited protection and raises concerns that vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness."
Redd adds, "Our findings suggest that HIV vaccine strategies designed to recreate the natural immune response to HIV may be insufficient to protect an individual from infection. However, the data also provide an interesting new population to explore since it is possible that some individuals will be protected from superinfection. Determining what controls this could lead to new avenues for vaccine research."
"The Rates of HIV Superinfection and Primary HIV Incidence in a General Population in Rakai, Uganda," was written by Andrew D. Redd, Caroline E. Mullis, David Serwadda, Xiangrong Kong, Craig Martens, Stacy M. Ricklefs, Aaron A. R. Tobian, Changchang Xiao, Mary K. Grabowski, Fred Nalugoda, Godfrey Kigozi, Oliver Laeyendecker, Joseph Kagaayi, Nelson Sewankambo, Ronald H. Gray, Stephen F. Porcella, Maria J. Wawer and Thomas C. Quinn.
The research was supported in part by the National Institutes of Health and the Bill and Melinda Gates Foundation.